Evidence review: Open Peptide Project (verified against primary PubMed, ClinicalTrials.gov & FDA records) · Last checked 2026-10-27. ← Back to Evidence Library

NNZ-2591 (cyclo-glycyl-2-allyl proline): what the evidence says

Name: NNZ-2591 (cyclo-glycyl-2-allyl proline)
Published: 2026-10-27

At a glance

What it is: a small synthetic cyclic dipeptide related to cyclic glycine-proline, a natural breakdown product of IGF-1. Developed by Neuren for rare neurodevelopmental disorders; not approved anywhere. ^{R1, R2}

What the evidence says: 🟨 in one open-label phase 2 study of 18 children with Phelan-McDermid syndrome, 16 were rated improved by clinicians, but there was no placebo group. ^R1 Placebo-controlled phase 3 trials are recruiting. ^{R3, R4}

Biggest risks: safety data come from small, short studies. Long-term risks are unknown. ^R1

Rating


Human Human evidence	Very limited: one open-label phase 2 published (n = 18) ^R1
Animal Animal / lab evidence	Not reviewed
Regulatory	Investigational; not FDA-approved · not on FDA's 503A or 503B bulk-substance category lists and not on FDA's compounding safety-risk page ^{R5, R6, R7} · not named by WADA ^R8
Established human dose	No (trial amounts only; see Study details)

Evidence verdict: Phelan-McDermid syndrome: Very limited (one 18-child open-label phase 2) · Pitt Hopkins and Angelman syndromes: Very limited (open-label phase 2, results not reviewed here) · Other uses: No human data

This page reports what studies used. It is not dosing advice.

Legend: HUMAN data · ANIMAL / LAB data · UNKNOWN · UNVERIFIED: not yet confirmed against a primary source

About the evidence: open-label studies without a placebo group can overstate benefit, especially when outcomes are clinician or caregiver ratings.

What is it?

Related pages: trofinetide, igf-1-mecasermin.

Does it work?

🟨 Phelan-McDermid (phase 2): 16 of 18 children improved on clinician global ratings; no placebo group. ^{R1, R2}
⚪ Pitt Hopkins and Angelman (phase 2): completed open-label studies; peer-reviewed results not found for this page. UNVERIFIED ^{R9, R10}
Prader-Willi: the planned phase 2 was withdrawn before enrolling anyone. ^R11

Is it safe?

🟨 Reported as generally well tolerated in the small phase 2 study. ^R1
Long-term and rare risks unknown.

Pipeline status (investigational)

Phase 1 completed. ^R12
Phase 2: Phelan-McDermid, Pitt Hopkins and Angelman completed; Prader-Willi withdrawn. ^{R2, R9, R10, R11}
Phase 3: two Phelan-McDermid trials recruiting (160 and 180 planned). ^{R3, R4}

Gray-market vials: extra risks

A gray-market vial has no quality control and no guarantee of identity, strength or sterility. We test retail vials blind under the Open Peptide Standard; see /tests/. A passing test covers one batch on one date and does not mean the compound is safe.

Is it legal?

US: investigational; not FDA-approved. No Drugs@FDA application found (openFDA searched Oct 27, 2026).
Compounding: not on FDA's 503A or 503B bulk-substance category lists and not on FDA's compounding safety-risk page. ^{R5, R6, R7}
Sport: not named on WADA's 2026 Prohibited List. ^R8

Study details

These are amounts researchers used, not recommendations.

Study	People / model	Route	Amount used	Follow-up	Reported	Citation
PMS-001 (Phelan-McDermid)	18 children	Oral	Per protocol	13 weeks, open-label	16 of 18 improved on CGI-I	PMID 41450730
NCT05025332 (Pitt Hopkins)	28 children	Oral	Per protocol	Open-label	Results not reviewed UNVERIFIED	^R9
NCT05011851 (Angelman)	17 children	Oral	Per protocol	Open-label	Results not reviewed UNVERIFIED	^R10

Full reference list (PubMed, CT.gov, FDA and WADA checked Oct 27, 2026)

^R1 Neumeyer AM, et al. Neurol Genet. 2026. PMID 41450730
^R2 ClinicalTrials.gov NCT05025241, open-label phase 2 in Phelan-McDermid syndrome, completed, 18 enrolled (CT.gov API v2, checked Oct 27, 2026). https://clinicaltrials.gov/study/NCT05025241
^R3 ClinicalTrials.gov NCT07281079, placebo-controlled phase 3 in Phelan-McDermid syndrome, recruiting, 160 planned (CT.gov API v2, checked Oct 27, 2026). https://clinicaltrials.gov/study/NCT07281079
^R4 ClinicalTrials.gov NCT07593391, phase 3 in Phelan-McDermid syndrome, recruiting, 180 planned (CT.gov API v2, checked Oct 27, 2026). https://clinicaltrials.gov/study/NCT07593391
^R5 FDA, 503A bulk drug substances categories list (updated May 14, 2026). https://www.fda.gov/media/94155/download
^R6 FDA, 503B bulk drug substances categories list (updated Mar 21, 2025). https://www.fda.gov/media/94164/download
^R7 FDA, Certain bulk drug substances for use in compounding that may present significant safety risks (content current Apr 22, 2026). https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
^R8 WADA. The 2026 Prohibited List, full list checked; compound not named. https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf
^R9 ClinicalTrials.gov NCT05025332, open-label phase 2 in Pitt Hopkins syndrome, completed, 28 enrolled (CT.gov API v2, checked Oct 27, 2026). https://clinicaltrials.gov/study/NCT05025332
^R10 ClinicalTrials.gov NCT05011851, open-label phase 2 in Angelman syndrome, completed, 17 enrolled (CT.gov API v2, checked Oct 27, 2026). https://clinicaltrials.gov/study/NCT05011851
^R11 ClinicalTrials.gov NCT05879614, open-label phase 2 in Prader-Willi syndrome, withdrawn before enrollment (CT.gov API v2, checked Oct 27, 2026). https://clinicaltrials.gov/study/NCT05879614
^R12 ClinicalTrials.gov NCT04379869, phase 1 study (CT.gov API v2, checked Oct 27, 2026). https://clinicaltrials.gov/study/NCT04379869

Disclaimer

This page is for education and harm reduction, not medical advice or a recommendation to use NNZ-2591 (cyclo-glycyl-2-allyl proline). This is an investigational drug. It is available only inside registered clinical trials; products sold online under this name are unregulated. Report problems to FDA MedWatch (https://www.fda.gov/safety/medwatch).